Fish Oil - Omega-3 Exerts Protective Effect in Oxidative Stress and Liver Dysfunctions Resulting from Experimental Sepsis.

Background: Sepsis is a severe global health problem, with high morbidity and mortality. In sepsis, one of the main affected organs is the liver. Hepatic alterations characterize a negative prognostic. Omega-3 fatty acids (ω3), eicosapentaenoic acid, and docosahexaenoic acid, are part of the main families of polyunsaturated fatty acids. ω3 has been used in studies as sepsis treatment and as a treatment for non-alcoholic liver disease. Aim: We aimed to evaluate the effects of treatment with fish oil (FO) rich in ω3 on liver changes and damage resulting from experimental sepsis. Methodology: A model of severe sepsis in Wistar rats was used. Oxidative stress in the liver tissue was evaluated by means of tests of thiobarbituric acid reactive substances, 2,7-dihydrodichlorofluorescein diacetate , catalase, and glutathione peroxidase, in the serum TBARS, DCF, thiols and, to assess liver dysfunction, alanine aminotransferase and aspartate aminotransferase. Hepatic tissue damage was evaluated using H&E histology. Results: In assessments of oxidative stress in liver tissue, a protective effect was observed in the tests of TBARS, DCF, CAT, and GPx, when compared the sepsis versus sepsis+ω3 groups. Regarding the oxidative stress in serum, a protective effect of treatment with ω3 was observed in the TBARS, DCF, and thiols assays, in the comparison between the sepsis and sepsis+ω3 groups. ω3 had also a beneficial effect on biochemical parameters in serum in the analysis of ALT, creatinine, urea, and lactate, observed in the comparison between the sepsis and sepsis+ω3 groups. Conclusion: The results suggest ω3 as a liver protector during sepsis with an antioxidant effect, alleviating injuries and dysfunctions.

Less is more: Enterobactin concentration dependency in copper tolerance and toxicity.

The ability of siderophores to play roles beyond iron acquisition has been recently proven for many of them and evidence continues to grow. An earlier work showed that the siderophore enterobactin is able to increase copper toxicity by reducing Cu2+ to Cu+, a form of copper that is more toxic to cells. Copper toxicity is multifaceted. It involves the formation of reactive oxygen species (ROS), mismetallation of enzymes and possibly other mechanisms. Given that we previously reported on the capacity of enterobactin to alleviate oxidative stress caused by various stressors other than copper, we considered the possibility that the siderophore could play a dual role regarding copper toxicity. In this work, we show a bimodal effect of enterobactin on copper toxicity (protective and harmful) which depends on the siderophore concentration. We found that the absence of enterobactin rendered Escherichia coli cells more sensitive to copper, due to the reduced ability of those cells to cope with the metal-generated ROS. Consistently, addition of low concentrations of the siderophore had a protective effect by reducing ROS levels. We observed that in order to achieve this protection, enterobactin had to enter cells and be hydrolyzed in the cytoplasm. Further supporting the role of enterobactin in oxidative stress protection, we found that both oxygen and copper, induced the expression of the siderophore and also found that copper strongly counteracted the well-known downregulation effect of iron on enterobactin synthesis. Interestingly, when enterobactin was present in high concentrations, cells became particularly sensitive to copper most likely due to the Cu2+ to Cu+ reduction, which increased the metal toxicity leading to cell death.

Current Medical Treatment for Alcohol-Associated Liver Disease.

Alcohol-associated liver disease is one of the main causes of chronic liver disease. It comprises a clinical-histologic spectrum of presentations, from steatosis, steatohepatitis, to different degrees of fibrosis, including cirrhosis and severe necroinflammatory disease, called alcohol-associated hepatitis. In this focused update, we aim to present specific therapeutic interventions and strategies for the management of alcohol-associated liver disease. Current evidence for management in all spectra of manifestations is derived from general chronic liver disease recommendations, but with a higher emphasis on abstinence and nutritional support. Abstinence should comprise the treatment of alcohol use disorder as well as withdrawal syndrome. Nutritional assessment should also consider the presence of sarcopenia and its clinical manifestation, frailty. The degree of compensation of the disease should be evaluated, and complications, actively sought. The most severe acute form of this disease is alcohol-associated hepatitis, which has high mortality and morbidity. Current treatment is based on corticosteroids that act by reducing immune activation and blocking cytotoxicity and inflammation pathways. Other aspects of treatment include preventing and treating hepatorenal syndrome as well as preventing infections although there is no clear evidence as to the benefit of probiotics and antibiotics in prophylaxis. Novel therapies for alcohol-associated hepatitis include metadoxine, interleukin-22 analogs, and interleukin-1-beta antagonists. Finally, granulocyte colony-stimulating factor, microbiota transplantation, and gut-liver axis modulation have shown promising results. We also discuss palliative care in advanced alcohol-associated liver disease.

Chronic hypoxemia induces mitochondrial respiratory complex gene expression in the fetal sheep brain.

Objective: The molecular pathways underlying hypoxemia-induced alterations in neurodevelopment of infants with congenital heart disease have not been delineated. We used transcriptome analysis to investigate differential gene expression induced by hypoxemia in an ovine artificial-womb model. Methods: Mid-gestation fetal sheep (median [interquartile range] 109 [107-112] days' gestation) were cannulated via the umbilical vessels, attached to a pumpless, low-resistance oxygenator circuit, and incubated in a sterile, fluid environment for 22 [21-23] days. Fetuses were maintained with an oxygen delivery of 20-25 mL/kg/min (normoxemia, n = 3) or 14-16 mL/kg/min (hypoxemia, n = 4). Transcriptional profiling by RNA sequencing was carried out on left frontal brains and hypoxemia-regulated genes were identified by differential gene expression analysis. Results: A total of 228 genes whose expression was up or down regulated by ≥1.5-fold (false discovery rate ≤0.05) were identified. The majority of these genes were induced in hypoxemic animals compared to normoxemic controls, and functional enrichment analysis identified respiratory electron transport as a pathway strongly upregulated in the brain during chronic hypoxemia. Further examination of hypoxemia-induced genes showed robust induction of all 7 subunits of the mitochondrial NADH:ubiquinone oxidoreductase (complex I). Other hypoxemia-induced genes included cytochrome B, a component of complex III, and ATP6, ATP8, both of which are components of complex V. Conclusions: Chronic fetal hypoxemia leads to upregulation of multiple mitochondrial respiratory complex genes critical for energy production and reactive oxygen species generation, including complex I. These data provide valuable insight into potential pathways involved in chronic hypoxemia-induced neuropathology and offers potential therapeutic targets for fetal neuroprotection in fetuses with congenital heart defects.

Lepidium meyenii (maca) and soy isoflavones reduce cardiac stunning of ischemia-reperfusion in rats by mitochondrial mechanisms.

BACKGROUND AND AIM: Phytoestrogens are traditionally used for cardiovascular risks but direct effects on the ischemic heart remain unclear. Plants with phytoestrogens are used for reducing menopausic symptoms and they could also be cardioprotectives. Here we investigated whether maca (Lepidium meyenii) contains isoflavones and prevents cardiac stunning, in comparison to soy isoflavones. EXPERIMENTAL PROCEDURE: Both products were orally and daily administered to rats during 1 week before exposing isolated hearts to ischemia/reperfusion (I/R). Young male (YM), female (YF) and aged female (AgF) rats treated with maca (MACA, 1 g/kg/day) or soy isoflavones (ISOF, 100 mg/kg/day) were compared to acute daidzein (DAZ, 5 mg/kg i.p.) and non-treated rat groups. Isolated ventricles were perfused inside a calorimeter to simultaneously measure contractile and calorimetrical signals before and during I/R. RESULTS AND CONCLUSIONS: Maca has genistein and daidzein. MACA and ISOF improved the post-ischemic contractile recovery (PICR) and muscle economy (P/Ht) in YM and YF hearts, but not in AgF hearts. DAZ improved PICR and P/Ht more in YM than in YF. The mKATP channels blockade reduced both PICR and P/Ht in DAZ-treated YM hearts, without affecting them in ISOF or MACA-treated YM hearts. In MACA treated YF hearts, the simultaneous blockade of NOS and mKATP channels, or the mNCX blockade reduced cardioprotection. Results show that subacute oral treatment with maca or with soy isoflavones was strongly preventive of cardiac ischemic dysfunction, more than the acute administration of a pure isoflavone (daidzein, genistein). Maca induced synergistic and complex mechanisms which prevented mitochondrial calcium overload.

Phytomodulatory proteins isolated from Calotropis procera latex promote glycemic control by improving hepatic mitochondrial function in HepG2 cells.

The medicinal uses of Calotropis procera are diverse, yet some of them are based on effects that still lack scientific support. Control of diabetes is one of them. Recently, latex proteins from C. procera latex (LP) have been shown to promote in vivo glycemic control by the inhibition of hepatic glucose production via AMP-activated protein kinase (AMPK). Glycemic control has been attributed to an isolated fraction of LP (CpPII), which is composed of cysteine peptidases (95%) and osmotin (5%) isoforms. Those proteins are extensively characterized in terms of chemistry, biochemistry and structural aspects. Furthermore, we evaluated some aspects of the mitochondrial function and cellular mechanisms involved in CpPII activity. The effect of CpPII on glycemic control was evaluated in fasting mice by glycemic curve and glucose and pyruvate tolerance tests. HepG2 cells was treated with CpPII, and cell viability, oxygen consumption, PPAR activity, production of lactate and reactive oxygen species, mitochondrial density and protein and gene expression were analyzed. CpPII reduced fasting glycemia, improved glucose tolerance and inhibited hepatic glucose production in control animals. Additionally, CpPII increased the consumption of ATP-linked oxygen and mitochondrial uncoupling, reduced lactate concentration, increased protein expression of mitochondrial complexes I, III and V, and activity of peroxisome-proliferator-responsive elements (PPRE), reduced the presence of reactive oxygen species (ROS) and increased mitochondrial density in HepG2 cells by activation of AMPK/PPAR. Our findings strongly support the medicinal use of the plant and suggest that CpPII is a potential therapy for prevention and/or treatment of type-2 diabetes. A common epitope sequence shared among the proteases and osmotin is possibly the responsible for the beneficial effects of CpPII.

Toxicity evaluation of Eleutherine plicata Herb. extracts and possible cell death mechanism.

Eleutherine plicata has been shown to be a promising medicinal plant, and its activity has been associated with naphthoquinones. The present study aimed at evaluating the cytotoxicity, genotoxicity, and oral toxicity of the ethanol extract (EEEp), dichloromethane fraction (FDMEp) of E. plicata, and isoeleutherin. For the cytotoxicity evaluation, the viability test (MTT) was used. Genotoxicity was accessed through the Comet assay (alkaline version), acute and subacute oral toxicities were also evaluated. The antioxidant capacity of the samples in the wells where the cells were treated with E. plicata was evaluated. Furthermore, the participation of caspase-8 in the possible mechanism of action of isoeleutherin, eleutherin, and eleutherol was also investigated through a docking study. FDMEp and isoeleutherin were cytotoxic, with higher rates of DNA fragmentation observed for FDMEp and isoeleutherin, and all samples displayed higher antioxidant potential than the control. In the acute oral toxicity test, EEEp, FDMEp, and isoeleutherin did not cause significant clinical changes. In the subacute toxicity assay, EEEp and FDMEp also did not cause clinical, hematological, or biochemical changes. The three compounds bound similarly to caspase-8. Despite the results of cytotoxicity, in vitro studies demonstrated that the use of EEEp appears to be safe and cell death may involve its binding to caspase-8.

Dysfunctional mitochondria as critical players in the inflammation of autoimmune diseases: Potential role in Sjögren's syndrome.

Relevant reviews highlight the association between dysfunctional mitochondria and inflammation, but few studies address the contribution of mitochondria and mitochondria-endoplasmic reticulum (ER) contact sites (MERCs) to cellular homeostasis and inflammatory signaling. The present review outlines the important role of mitochondria in cellular homeostasis and how dysfunctional mitochondrion can release and misplace mitochondrial components (cardiolipin, mitochondrial DNA (mtDNA), and mitochondrial formylated peptides) through multiple mechanisms. These components can act as damage-associated molecular patterns (DAMPs) and induce an inflammatory response via pattern recognition receptors (PRRs). Accumulation of damaged ROS-generating mitochondria, accompanied by the release of mitochondrial DAMPs, can activate PRRs such as the NLRP3 inflammasome, TLR9, cGAS/STING, and ZBP1. This process would explain the chronic inflammation that is observed in autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type I diabetes (T1D), and Sjögren's syndrome. This review also provides a comprehensive overview of the importance of MERCs to mitochondrial function and morphology, cellular homeostasis, and the inflammatory response. MERCs play an important role in calcium homeostasis by mediating the transfer of calcium from the ER to the mitochondria and thereby facilitating the production of ATP. They also contribute to the synthesis and transfer of phospholipids, protein folding in the ER, mitochondrial fission, mitochondrial fusion, initiation of autophagosome formation, regulation of cell death/survival signaling, and regulation of immune responses. Therefore, alterations within MERCs could increase inflammatory signaling, modulate ER stress responses, cell homeostasis, and ultimately, the cell fate. This study shows severe ultrastructural alterations of mitochondria in salivary gland cells from Sjögren's syndrome patients for the first time, which could trigger alterations in cellular bioenergetics. This finding could explain symptoms such as fatigue and malfunction of the salivary glands in Sjögren's syndrome patients, which would contribute to the chronic inflammatory pathology of the disease. However, this is only a first step in solving this complex puzzle, and several other important factors such as changes in mitochondrial morphology, functionality, and their important contacts with other organelles require further in-depth study. Future work should focus on detecting the key milestones that are related to inflammation in patients with autoimmune diseases, such as Sjögren´s syndrome.

Application of green synthesised copper iodide particles on cotton fabric-protective face mask material against COVID-19 pandemic.

Microorganisms cause variety of diseases that constitutes a severe threat to mankind. Due to the upsurge of many infectious diseases, there is a high requirement and demand for the development of safety products finished with antimicrobial properties. The study involves the antimicrobial activity of natural cotton coated with copper iodide capped with Hibiscus rosa-sinensis L. flower extract (CuI-FE) which is rich in anthocyanin, cyanidin-3-sophoroside by ultrasonication method. The coated and uncoated cotton fabric was characterised through XRD, SEM, AFM, tensile strength and UV-Visible spectroscopic techniques. XRD confirmed the formation of CuI particles, SEM showed that CuI-FE was prismatic in shape. The average size of CuI-FE particles was found to be 552.45 nm. Anti-bacterial studies showed copper iodide particles to be a potent antimicrobial agent. AFM images confirmed the rupture of bacterial cell walls in the presence of prismatic CuI-FE. In-vitro cytotoxicity investigation of CuI-FE was performed against cancer and spleen cell lines to evaluate the cell viability. Cytotoxicity analysis revealed the IC50 value of 233.93 µg/mL in the presence of CuI-FE. Molecular docking study was also carried out to understand the interaction of CuI-FE with COVID-19 main protease. This paper has given an insight on the usage of CuI-FE coated on the cotton fabric that has proved to have strong inhibition against the nano ranged bacterial, cancerous cell line and a strong interaction with the COVID-19 protease. Such eco-friendly material will provide a safe environment even after the disposable of medical waste from the infectious diseases like influenza and current pandemic like COVID-19.

The potential role of sesquiterpene lactones isolated from medicinal plants in the treatment of the metabolic syndrome - A review.

Metabolic syndrome comprises a cluster of metabolic disorders related to the development of cardiovascular disease and type 2 diabetes mellitus. In latter years, plant secondary metabolites have become of special interest because of their potential role in preventing and managing metabolic syndrome. Sesquiterpene lactones constitute a large and diverse group of biologically active compounds widely distributed in several medicinal plants used for the treatment of metabolic disorders. The structural diversity and the broad spectrum of biological activities of these compounds drew significant interests in the pharmacological applications. This review describes selected sesquiterpene lactones that have been experimentally validated for their biological activities related to risk factors of metabolic syndrome, together with their mechanisms of action. The potential beneficial effects of sesquiterpene lactones discussed in this review demonstrate that these substances represent remarkable compounds with a diversity of molecular structure and high biological activity, providing new insights into the possible role in metabolic syndrome management.

Analysis of urinary VOCs using mass spectrometric methods to diagnose cancer: A review.

The development of non-invasive screening techniques for early cancer detection is one of the greatest scientific challenges of the 21st century. One promising emerging method is the analysis of volatile organic compounds (VOCs). VOCs are low molecular weight substances generated as final products of cellular metabolism and emitted through a variety of biological matrices, such as breath, blood, saliva and urine. Urine stands out for its non-invasive nature, availability in large volumes, and the high concentration of VOCs in the kidneys. This review provides an overview of the available data on urinary VOCs that have been investigated in cancer-focused clinical studies using mass spectrometric (MS) techniques. A literature search was conducted in ScienceDirect, Pubmed and Web of Science, using the keywords "Urinary VOCs", "VOCs biomarkers" and "Volatile cancer biomarkers" in combination with the term "Mass spectrometry". Only studies in English published between January 2011 and May 2020 were selected. The three most evaluated types of cancers in the reviewed studies were lung, breast and prostate, and the most frequently identified urinary VOC biomarkers were hexanal, dimethyl disulfide and phenol; with the latter seeming to be closely related to breast cancer. Additionally, the challenges of analyzing urinary VOCs using MS-based techniques and translation to clinical utility are discussed. The outcome of this review may provide valuable information to future studies regarding cancer urinary VOCs.

Efeito do Enterococcus faecium e Saccharomyces cerevisiae na resposta imunológica, parâmetros hematológicos e ganho de peso de bezerros alimentados com silagem de milho / Effect of the Enterococcus faecium and Saccharomyces cerevisiae in the immunological response, hematological parameters and body weight of calves fed with corn silage / Efecto de Enterococcus faecium y Saccharomyces cerevisiae en la respuesta inmunológica, parámetros hematológicos y ganancia de peso de terneros alimentados con ensilaje de maíz

O uso de probióticos a base de leveduras melhora o ganho de peso e o sistema imunológico de bovinos frente a grandes desafios imunológicos, no entanto permanece a dúvida se seu uso também apresentaria efeito em desafios mais tênues. Desta maneira, o presente trabalho verificou se o uso de probiótico a base de Enterococcus faecium e Saccaromyces cerevisiae via oral interfere na imunidade inata e no peso de bezerros sadios, em fase de crescimento, alimentados principalmente com silagem de milho. Para tanto, 12 bezerros da raça Jersey (120 kg ±50 kg e 4-7 meses de idade), foram alocados nos grupos controle (n=6) ou tratamento (n=6), de acordo com a oferta de probiótico (2g/dia, via oral) durante 45 dias. Nos dias 0, 15, 30 e 45, os animais foram submetidos a pesagens, exames clínicos, e colheita de sangue para realização de hemograma e mensuração do metabolismo oxidativo neutrofílico. Observou-se que, o probiótico promoveu pequeno e pontual incremento na função neutrofilica sanguínea (P=0,10, D15), incremento nos valores de hematócrito e hemoglobina (P=0,03 e 0,05, D45), além de maior ganho de peso nas fases iniciais da administração do suplemento (P=0,05), permitindo concluir que o suplemento é benéfico para animais em fase de adaptação de trocas de dieta e de manejo, mesmo quando estes desafios são tênues.(AU)

The use of yeast probiotics improves body weight gain and the immune system of cattle submitted to husbandry challenges, however the question remains whether the probiotics could have an effect on more tenuous challenges. In this way, the present study verified if the use of probiotic (Enterococcus faecium and Saccharomyces cerevisiae) provided orally, interferes with the innate immunity and body weight of calves fed mainly with corn silage. Twelve Jersey calves (120 kg ± 50 kg and 4-7 months of age) were allocated to the control (n = 6) or treatment (n = 6) group according to the probiotic supply (2 g / day, orally) for 45 days. On days 0, 15, 30 and 45, the animals were weighted, and submitted to clinical examinations, and blood collection for hemogram and measurement of neutrophil oxidative metabolism. It was observed that the probiotic promoted a slight and punctual increase in blood neutrophilic function (P = 0.10, D15), increased hematocrit and hemoglobin values P = 0.03 and 0.05, D45) and increased the body weight gain in the initial phases of supplementation (P = 0.08), allowing to conclude that the probiotic is beneficial for animals in the adaptation phase of diet changes and management, even when these challenges are mild.(AU)

El uso de probióticos de levadura mejora el aumento de peso corporal y el sistema inmunológico del ganado sometido a los desafíos de la cría, sin embargo, la pregunta sigue siendo si los probióticos podrían tener un efecto en desafíos más tenues. De esta manera, el presente estudio verificó si el uso de probióticos (Enterococcus faecium y Saccharomyces cerevisiae) proporcionado por vía oral interfiere con la inmunidad innata y el peso corporal de los terneros alimentados principalmente con ensilaje de maíz. Doce terneros de Jersey (120 kg ± 50 kg y 4-7 meses de edad) se asignaron al grupo control (n = 6) o tratamiento (n = 6) según el suministro de probióticos (2 g / día, por vía oral) para 45 dias. En los días 0, 15, 30 y 45, los animales se pesaron y se sometieron a exámenes clínicos y se recogieron muestras de sangre para el hemograma y la medición del metabolismo oxidativo de los neutrófilos. Se observó que el probiótico promovió un aumento leve y puntual de la función neutrofílica en sangre (P = 0,10, D15), aumento de los valores de hematocrito y hemoglobina (P = 0,03 y 0,05, D45) y aumento de la ganancia de peso corporal en las fases iniciales de la suplementación. (P = 0.08), lo que permite concluir que el probiótico es beneficioso para los animales en la fase de adaptación de los cambios y el manejo de la dieta, incluso cuando estos desafíos son leves.(AU)

Efeito do Enterococcus faecium e Saccharomyces cerevisiae na resposta imunológica, parâmetros hematológicos e ganho de peso de bezerros alimentados com silagem de milho / Effect of the Enterococcus faecium and Saccharomyces cerevisiae in the immunological response, hematological parameters and body weight of calves fed with corn silage / Efecto de Enterococcus faecium y Saccharomyces cerevisiae en la respuesta inmunológica, parámetros hematológicos y ganancia de peso de terneros alimentados con ensilaje de maíz

O uso de probióticos a base de leveduras melhora o ganho de peso e o sistema imunológico de bovinos frente a grandes desafios imunológicos, no entanto permanece a dúvida se seu uso também apresentaria efeito em desafios mais tênues. Desta maneira, o presente trabalho verificou se o uso de probiótico a base de Enterococcus faecium e Saccaromyces cerevisiae via oral interfere na imunidade inata e no peso de bezerros sadios, em fase de crescimento, alimentados principalmente com silagem de milho. Para tanto, 12 bezerros da raça Jersey (120 kg ±50 kg e 4-7 meses de idade), foram alocados nos grupos controle (n=6) ou tratamento (n=6), de acordo com a oferta de probiótico (2g/dia, via oral) durante 45 dias. Nos dias 0, 15, 30 e 45, os animais foram submetidos a pesagens, exames clínicos, e colheita de sangue para realização de hemograma e mensuração do metabolismo oxidativo neutrofílico. Observou-se que, o probiótico promoveu pequeno e pontual incremento na função neutrofilica sanguínea (P=0,10, D15), incremento nos valores de hematócrito e hemoglobina (P=0,03 e 0,05, D45), além de maior ganho de peso nas fases iniciais da administração do suplemento (P=0,05), permitindo concluir que o suplemento é benéfico para animais em fase de adaptação de trocas de dieta e de manejo, mesmo quando estes desafios são tênues.

The use of yeast probiotics improves body weight gain and the immune system of cattle submitted to husbandry challenges, however the question remains whether the probiotics could have an effect on more tenuous challenges. In this way, the present study verified if the use of probiotic (Enterococcus faecium and Saccharomyces cerevisiae) provided orally, interferes with the innate immunity and body weight of calves fed mainly with corn silage. Twelve Jersey calves (120 kg ± 50 kg and 4-7 months of age) were allocated to the control (n = 6) or treatment (n = 6) group according to the probiotic supply (2 g / day, orally) for 45 days. On days 0, 15, 30 and 45, the animals were weighted, and submitted to clinical examinations, and blood collection for hemogram and measurement of neutrophil oxidative metabolism. It was observed that the probiotic promoted a slight and punctual increase in blood neutrophilic function (P = 0.10, D15), increased hematocrit and hemoglobin values P = 0.03 and 0.05, D45) and increased the body weight gain in the initial phases of supplementation (P = 0.08), allowing to conclude that the probiotic is beneficial for animals in the adaptation phase of diet changes and management, even when these challenges are mild.

El uso de probióticos de levadura mejora el aumento de peso corporal y el sistema inmunológico del ganado sometido a los desafíos de la cría, sin embargo, la pregunta sigue siendo si los probióticos podrían tener un efecto en desafíos más tenues. De esta manera, el presente estudio verificó si el uso de probióticos (Enterococcus faecium y Saccharomyces cerevisiae) proporcionado por vía oral interfiere con la inmunidad innata y el peso corporal de los terneros alimentados principalmente con ensilaje de maíz. Doce terneros de Jersey (120 kg ± 50 kg y 4-7 meses de edad) se asignaron al grupo control (n = 6) o tratamiento (n = 6) según el suministro de probióticos (2 g / día, por vía oral) para 45 dias. En los días 0, 15, 30 y 45, los animales se pesaron y se sometieron a exámenes clínicos y se recogieron muestras de sangre para el hemograma y la medición del metabolismo oxidativo de los neutrófilos. Se observó que el probiótico promovió un aumento leve y puntual de la función neutrofílica en sangre (P = 0,10, D15), aumento de los valores de hematocrito y hemoglobina (P = 0,03 y 0,05, D45) y aumento de la ganancia de peso corporal en las fases iniciales de la suplementación. (P = 0.08), lo que permite concluir que el probiótico es beneficioso para los animales en la fase de adaptación de los cambios y el manejo de la dieta, incluso cuando estos desafíos son leves.

Primary targets of the sesquiterpene lactone deoxymikanolide on Trypanosoma cruzi.

BACKGROUND: Deoxymikanolide is a sesquiterpene lactone isolated from Mikania micrantha and M. variifolia which, has previously demonstrated in vitro activity on Trypanosoma cruzi and in vivo activity on an infected mouse model. PURPOSE: Based on these promising findings, the aim of this study was to investigate the mechanism of action of this compound on different parasite targets. METHODS: The interaction of deoxymikanolide with hemin was examined under reducing and non- reducing conditions by measuring modifications in the Soret absorption band of hemin; the thiol interaction was determined spectrophotometrically through its reaction with 5,5'-dithiobis-2-nitrobenzoate in the presence of glutathione; activity on the parasite antioxidant system was evaluated by measuring the activity of the superoxide dismutase and trypanothione reductase enzymes, together with the intracellular oxidative state by flow cytometry. Superoxide dismutase and trypanothione reductase activities were spectrophotometrically tested. Cell viability, phosphatidylserine exposure and mitochondrial membrane potential were assessed by means of propidium iodide, annexin-V and rhodamine 123 staining, respectively; sterols were qualitatively and quantitatively tested by TLC; ultrastructural changes were analyzed by transmission electron microscopy. Autophagic cells were detected by staining with monodansylcadaverine. RESULTS: Deoxymikanolide decreased the number of reduced thiol groups within the parasites, which led to their subsequent vulnerability to oxidative stress. Treatment of the parasites with the compound produced a depolarization of the mitochondrial membrane even though the plasma membrane permeabilization was not affected. Deoxymikanolide did not affect the intracellular redox state and so the mitochondrial dysfunction produced by this compound could not be attributed to ROS generation. The antioxidant defense system was affected by deoxymikanolide at twenty four hours of treatment, when both an increased oxidative stress and decreased activity of superoxide dismutase and trypanothione reductase (40 and 60% respectively) were observed. Both the oxidative stress and mitochondrial dysfunction induce parasite death by apoptosis and autophagy. CONCLUSION: Based on our results, deoxymikanolide would exert its anti-T cruzi activity as a strong thiol blocking agent and by producing mitochondrial dysfunction.

Efecto de Enterococcus faecium y Saccharomyces cerevisiae en la respuesta inmunológica, parámetros hematológicos y ganancia de peso de terneros alimentados con ensilaje de maíz. / Effect of the Enterococcus faecium and Saccharomyces cerevisiae in the immunological response, hematological parameters and body weight of calves fed with corn silage. / Efeito do Enterococcus faecium e Saccharomyces cerevisiae na resposta imunológica, parâmetros hematológicos e ganho de peso de bezerros alimentados com silagem de milho.

El uso de probióticos de levadura mejora el aumento de peso corporal y el sistema inmunológico del ganado sometido a los desafíos de la cría, sin embargo, la pregunta sigue siendo si los probióticos podrían tener un efecto en desafíos más tenues. De esta manera, el presente estudio verificó si el uso de probióticos (Enterococcus faecium y Saccharomyces cerevisiae) proporcionado por vía oral interfiere con la inmunidad innata y el peso corporal de los terneros alimentados principalmente con ensilaje de maíz. Doce terneros de Jersey (120 kg ± 50 kg y 4-7 meses de edad) se asignaron al grupo control (n = 6) o tratamiento (n = 6) según el suministro de probióticos (2 g / día, por vía oral) para 45 dias. En los días 0, 15, 30 y 45, los animales se pesaron y se sometieron a exámenes clínicos y se recogieron muestras de sangre para el hemograma y la medición del metabolismo oxidativo de los neutrófilos. Se observó que el probiótico promovió un aumento leve y puntual de la función neutrofílica en sangre (P = 0,10, D15), aumento de los valores de hematocrito y hemoglobina (P = 0,03 y 0,05, D45) y aumento de la ganancia de peso corporal en las fases iniciales de la suplementación. (P = 0.08), lo que permite concluir que el probiótico es beneficioso para los animales en la fase de adaptación de los cambios y el manejo de la dieta, incluso cuando estos desafíos son leves.

The use of yeast probiotics improves body weight gain and the immune system of cattle submitted to husbandry challenges, however the question remains whether the probiotics could have an effect on more tenuous challenges. In this way, the present study verified if the use of probiotic (Enterococcus faecium and Saccharomyces cerevisiae) provided orally, interferes with the innate immunity and body weight of calves fed mainly with corn silage. Twelve Jersey calves (120 kg ± 50 kg and 4-7 months of age) were allocated to the control (n = 6) or treatment (n = 6) group according to the probiotic supply (2 g / day, orally) for 45 days. On days 0, 15, 30 and 45, the animals were weighted, and submitted to clinical examinations, and blood collection for hemogram and measurement of neutrophil oxidative metabolism. It was observed that the probiotic promoted a slight and punctual increase in blood neutrophilic function (P = 0.10, D15), increased hematocrit and hemoglobin values (P = 0.03 and 0.05, D45) and increased the body weight gain in the initial phases of supplementation (P = 0.08), allowing to conclude that the probiotic is beneficial for animals in the adaptation phase of diet changes and management, even when these challenges are mild.

O uso de probióticos a base de leveduras melhora o ganho de peso e o sistema imunológico de bovinos frente a grandes desafios imunológicos, no entanto permanece a dúvida se seu uso também apresentaria efeito em desafios mais tênues. Desta maneira, o presente trabalho verificou se o uso de probiótico a base de Enterococcus faecium e Saccaromyces cerevisiae via oral interfere na imunidade inata e no peso de bezerros sadios, em fase de crescimento, alimentados principalmente com silagem de milho. Para tanto, 12 bezerros da raça Jersey (120 kg ±50 kg e 4-7 meses de idade), foram alocados nos grupos controle (n=6) ou tratamento (n=6), de acordo com a oferta de probiótico (2g/dia, via oral) durante 45 dias. Nos dias 0, 15, 30 e 45, os animais foram submetidos a pesagens, exames clínicos, e colheita de sangue para realização de hemograma e mensuração do metabolismo oxidativo neutrofílico. Observou-se que, o probiótico promoveu pequeno e pontual incremento na função neutrofilica sanguínea (P=0,10, D15), incremento nos valores de hematócrito e hemoglobina (P=0,03 e 0,05, D45), além de maior ganho de peso nas fases iniciais da administração do suplemento (P=0,05), permitindo concluir que o suplemento é benéfico para animais em fase de adaptação de trocas de dieta e de manejo, mesmo quando estes desafios são tênues.

Reactive oxygen species and antioxidant properties from mushrooms.

Preventive medicine and food industry have shown an increased interest in the development of natural antioxidants, since those most commonly used synthetic antioxidants may have restricted use in food. This could explain why there is currently much research on the antioxidant properties from natural products such as mushrooms. Many mushrooms have been reported to possess antioxidant properties, which enable them to neutralize free radicals. The oxygen molecule is a free radical, which lead to the generation of the reactive oxygen species and can damage the cells. Cell damage caused by free radicals appears to be a major contributor to aging and degenerative diseases. Mushrooms antioxidant components are found in fruit bodies, mycelium and culture both, which include polysaccharides, tocopherols, phenolics, carotenoids, ergosterol and ascorbic acid among others. Fruit bodies or mycelium can be manipulated to produce active compounds in a relatively short period of time, which represent a significant advantage in antioxidant compounds extraction from mushrooms. Antioxidant compounds may be extracted to be used as functional additives or mushrooms can be incorporated into our food regime, representing an alternative source of food to prevent damage caused by oxidation in the human body.

Oxidative profile exhibited by Mucopolysaccharidosis type IVA patients at diagnosis: Increased keratan urinary levels.

Morquio A disease (Mucopolysaccharidosis type IVA, MPS IVA) is one of the 11 mucopolysaccharidoses (MPSs), a heterogeneous group of inherited lysosomal storage disorders (LSDs) caused by deficiency in enzymes need to degrade glycosaminoglycans (GAGs). Morquio A is characterized by a decrease in N-acetylgalactosamine-6-sulfatase activity and subsequent accumulation of keratan sulfate and chondroitin 6-sulfate in cells and body fluids. As the pathophysiology of this LSD is not completely understood and considering the previous results of our group concerning oxidative stress in Morquio A patients receiving enzyme replacement therapy (ERT), the aim of this study was to investigate oxidative stress parameters in Morquio A patients at diagnosis. It was studied 15 untreated Morquio A patients, compared with healthy individuals. The affected individuals presented higher lipid peroxidation, assessed by urinary 15-F2t-isoprostane levels and no protein damage, determined by sulfhydryl groups in plasma and di-tyrosine levels in urine. Furthermore, Morquio A patients showed DNA oxidative damage in both pyrimidines and purines bases, being the DNA damage positively correlated with lipid peroxidation. In relation to antioxidant defenses, affected patients presented higher levels of reduced glutathione (GSH) and increased activity of glutathione peroxidase (GPx), while superoxide dismutase (SOD) and glutathione reductase (GR) activities were similar to controls. Our findings indicate that Morquio A patients present at diagnosis redox imbalance and oxidative damage to lipids and DNA, reinforcing the idea about the importance of antioxidant therapy as adjuvant to ERT, in this disorder.

Mitochondrial involvement in memory impairment induced by scopolamine in rats.

OBJECTIVE: Scopolamine (SCO) administration to rats induces molecular features of AD and other dementias, including impaired cognition, increased oxidative stress, and imbalanced cholinergic transmission. Although mitochondrial dysfunction is involved in different types of dementias, its role in cognitive impairment induced by SCO has not been well elucidated. The aim of this work was to evaluate the in vivo effect of SCO on different brain mitochondrial parameters in rats to explore its neurotoxic mechanisms of action. METHODS: Saline (Control) or SCO (1 mg/kg) was administered intraperitoneally 30 min prior to neurobehavioral and biochemical evaluations. Novel object recognition and Y-maze paradigms were used to evaluate the impact on memory, while redox profiles in different brain regions and the acetylcholinesterase (AChE) activity of the whole brain were assessed to elucidate the amnesic mechanism of SCO. Finally, the effects of SCO on brain mitochondria were evaluated both ex vivo and in vitro, the latter to determine whether SCO could directly interfere with mitochondrial function. RESULTS: SCO administration induced memory deficit, increased oxidative stress, and increased AChE activities in the hippocampus and prefrontal cortex. Isolated brain mitochondria from rats administered with SCO were more vulnerable to mitochondrial swelling, membrane potential dissipation, H2O2 generation and calcium efflux, all likely resulting from oxidative damage. The in vitro mitochondrial assays suggest that SCO did not affect the organelle function directly. CONCLUSION: In conclusion, the present results indicate that SCO induced cognitive dysfunction and oxidative stress may involve brain mitochondrial impairment, an important target for new neuroprotective compounds against AD and other dementias.

Biochemical and molecular modulation of CCl4-induced peripheral and central damage by Tilia americana var. mexicanaextracts.

Around the world, species from the genus Tilia are commonly used because of their peripheral and central medicinal effects; they are prepared as teas and used as tranquilizing, anticonvulsant, and analgesic agents. In this study, we provide evidence of the protective effects of organic and aqueous extracts (100 mg/kg, i.p.) obtained from the leaves of Tilia americana var. mexicana on CCl4-induced liver and brain damage in the rat. Protection was observed in the liver and brain (cerebellum, cortex and cerebral hemispheres) by measuring the activity of antioxidant enzymes and levels of malondialdehyde (MDA) using spectrophotometric methods. Biochemical parameters were also assessed in serum samples from the CCl4-treated rats. The T. americana var. mexicana leaf extracts provided significant protection against CCl4-induced peripheral and central damage by increasing the activity of antioxidant enzymes, diminishing lipid peroxidation, and preventing alterations in biochemical serum parameters, such as the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-globulin (γ-GLOB), serum albumin (ALB), total bilirubin (BB), creatinine (CREA) and creatine kinase (CK), relative to the control group. Additionally, we correlated gene expression with antioxidant activity in the experimental groups treated with the organic and aqueous Tilia extracts and observed a non-statistically significant positive correlation. Our results provide evidence of the underlying biomedical properties of T. americana var. mexicana that confer its neuro- and hepatoprotective effects.

Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders.

Reactive species play an important role in physiological functions. Overproduction of reactive species, notably reactive oxygen (ROS) and nitrogen (RNS) species along with the failure of balance by the body's antioxidant enzyme systems results in destruction of cellular structures, lipids, proteins, and genetic materials such as DNA and RNA. Moreover, the effects of reactive species on mitochondria and their metabolic processes eventually cause a rise in ROS/RNS levels, leading to oxidation of mitochondrial proteins, lipids, and DNA. Oxidative stress has been considered to be linked to the etiology of many diseases, including neurodegenerative diseases (NDDs) such as Alzheimer diseases, Amyotrophic lateral sclerosis, Friedreich's ataxia, Huntington's disease, Multiple sclerosis, and Parkinson's diseases. In addition, oxidative stress causing protein misfold may turn to other NDDs include Creutzfeldt-Jakob disease, Bovine Spongiform Encephalopathy, Kuru, Gerstmann-Straussler-Scheinker syndrome, and Fatal Familial Insomnia. An overview of the oxidative stress and mitochondrial dysfunction-linked NDDs has been summarized in this review.